Previous studies from this laboratory as well as others have demonstrated that acid protease inhibitors such as pepstatin can reduce or prevent ascites fluid accumulation in mice carrying five different tumor lines of ascites-producing tumors. In view of the potential benefits of pepstatin or related agents for therapy of ascites in humans as well as its use as a tool for elucidating the mechanism of ascites fluid accumulation, studies will be continued along two major lines of investigation. One will expand on our current knowledge of pepstatin's pharmacologic action in murine models of ascites by exploring the potency of the drug's action by administration under different conditions than heretofore used and comparing the results with known effects of the current protocol. In addition, analogues of pepstatin which differ in their inhibition profiles of proteases than does pepstatin will be tested for their ascites retardant activity and compared with pepstatin. In an attempt to bring murine models into close relevance with human models, slow growing murine tumor models which produce ascites (such as the A-10 adenocarcinoma) will be utilized for the first time. These models will allow withdrawal of ascites followed by administration of anti-protease agents. In the second line of investigation, studies on the mechanism of ascites accumulation will be continued. Observations on ascites retardant administration and its relationship to levels of pharmacological peptide generating systems such as leukokinins will be studied. In addition the isolation and purification of the components of murine and human ascites leukokinin-generating systems will be attempted in order to characterize the chemical and pharmacological components of the system.